Role of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsis

Summary: Extracellular miRNAs (ex-miRNAs) mediate intercellular communication and play a role in diverse physiological and pathological processes. Using small RNA sequencing, we identify that miRNAs are the most abundant RNA species in the plasma and differentially expressed in murine and human seps...

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Autores principales:	Sheng Wang, Yang Yang, Andrew Suen, Jing Zhu, Brittney Williams, Jiang Hu, Fengqian Chen, Rosemary Kozar, Shiqian Shen, Ziyi Li, Anjana Jeyaram, Steven M. Jay, Lin Zou, Wei Chao
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Molecular biology Immunology Cell biology Science Q
Acceso en línea:	https://doaj.org/article/ecd205c2503c41b38a4ba374510447a3
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spelling	oai:doaj.org-article:ecd205c2503c41b38a4ba374510447a32021-11-26T04:37:58ZRole of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsis2589-004210.1016/j.isci.2021.103441https://doaj.org/article/ecd205c2503c41b38a4ba374510447a32021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221014127https://doaj.org/toc/2589-0042Summary: Extracellular miRNAs (ex-miRNAs) mediate intercellular communication and play a role in diverse physiological and pathological processes. Using small RNA sequencing, we identify that miRNAs are the most abundant RNA species in the plasma and differentially expressed in murine and human sepsis, such as miR-146a-5p. Exogenous miR-146a-5p, but not its duplex precursor, induces a strong immunostimulatory response through a newly identified UU-containing motif and TLR7 activation, and an immunotolerance by rapid IRAK-1 protein degradation via TLR7→MyD88 signaling and proteasome activation, whereas its duplex precursor acts by targeting 3′ UTR of Irak-1 gene via Ago2 binding. miR-146a knockout in mice offers protection against sepsis with attenuated interleukin-6 (IL-6) storm and organ injury, improved cardiac function, and better survival. In septic patients, the plasma miR-146a-5p concentrations are closely associated with the two sepsis outcome predictors, blood lactate and coagulopathy. These data demonstrate the importance of extracellular miR-146a-5p in innate immune regulation and sepsis pathogenesis.Sheng WangYang YangAndrew SuenJing ZhuBrittney WilliamsJiang HuFengqian ChenRosemary KozarShiqian ShenZiyi LiAnjana JeyaramSteven M. JayLin ZouWei ChaoElsevierarticleMolecular biologyImmunologyCell biologyScienceQENiScience, Vol 24, Iss 12, Pp 103441- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Molecular biology Immunology Cell biology Science Q
spellingShingle	Molecular biology Immunology Cell biology Science Q Sheng Wang Yang Yang Andrew Suen Jing Zhu Brittney Williams Jiang Hu Fengqian Chen Rosemary Kozar Shiqian Shen Ziyi Li Anjana Jeyaram Steven M. Jay Lin Zou Wei Chao Role of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsis
description	Summary: Extracellular miRNAs (ex-miRNAs) mediate intercellular communication and play a role in diverse physiological and pathological processes. Using small RNA sequencing, we identify that miRNAs are the most abundant RNA species in the plasma and differentially expressed in murine and human sepsis, such as miR-146a-5p. Exogenous miR-146a-5p, but not its duplex precursor, induces a strong immunostimulatory response through a newly identified UU-containing motif and TLR7 activation, and an immunotolerance by rapid IRAK-1 protein degradation via TLR7→MyD88 signaling and proteasome activation, whereas its duplex precursor acts by targeting 3′ UTR of Irak-1 gene via Ago2 binding. miR-146a knockout in mice offers protection against sepsis with attenuated interleukin-6 (IL-6) storm and organ injury, improved cardiac function, and better survival. In septic patients, the plasma miR-146a-5p concentrations are closely associated with the two sepsis outcome predictors, blood lactate and coagulopathy. These data demonstrate the importance of extracellular miR-146a-5p in innate immune regulation and sepsis pathogenesis.
format	article
author	Sheng Wang Yang Yang Andrew Suen Jing Zhu Brittney Williams Jiang Hu Fengqian Chen Rosemary Kozar Shiqian Shen Ziyi Li Anjana Jeyaram Steven M. Jay Lin Zou Wei Chao
author_facet	Sheng Wang Yang Yang Andrew Suen Jing Zhu Brittney Williams Jiang Hu Fengqian Chen Rosemary Kozar Shiqian Shen Ziyi Li Anjana Jeyaram Steven M. Jay Lin Zou Wei Chao
author_sort	Sheng Wang
title	Role of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsis
title_short	Role of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsis
title_full	Role of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsis
title_fullStr	Role of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsis
title_full_unstemmed	Role of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsis
title_sort	role of extracellular microrna-146a-5p in host innate immunity and bacterial sepsis
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/ecd205c2503c41b38a4ba374510447a3
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_version_	1718409875229245440

Role of extracellular microRNA-146a-5p in host innate immunity and bacterial sepsis

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